CN103211833A - Application of icariin in preparation of medicaments for treating gout - Google Patents
Application of icariin in preparation of medicaments for treating gout Download PDFInfo
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- CN103211833A CN103211833A CN2013101498560A CN201310149856A CN103211833A CN 103211833 A CN103211833 A CN 103211833A CN 2013101498560 A CN2013101498560 A CN 2013101498560A CN 201310149856 A CN201310149856 A CN 201310149856A CN 103211833 A CN103211833 A CN 103211833A
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Abstract
The invention discloses an application of icariin in preparation of medicaments for treating gout. According to the application disclosed by the invention, the icariin is used for preparing the anti-gout medicaments, and animal experiments prove that a pharmaceutical composition prepared from the icariin can prevent and treat gouty arthritis, including acute gouty arthritis and chronic gouty arthritis. The material is wide in sources and easy to obtain, and the icariin is simple and easy to be used for preparing the medicaments and good in treatment effects.
Description
Technical field
The present invention relates to pharmaceutical field, the application of especially a kind of icariin in preparation treatment gout medicine.
Background technology
Gout is that its sickness rate increased year by year due to purine metabolic disturbance and urate excretion reduced.The sickness rate difference of various countries, nearly 10 annual morbidities in Asia rise gradually.Foreign data shows that the sickness rate of adult's hyperuricemia is up to 5%, and the prevalence of gout reaches 0.13%-0.37%.Along with improving constantly of China people people life level, people's dietary structure has very big change, high purine, high protein, higher fatty acid.Enter 21 century, goat has become the human second largest metabolic disease after diabetes.Clinical characters is: hyperuricemia, acute arthritis are shown effect repeatedly, tophus formation, chronic arthritis and joint deformity, and urate calculus and gouty parenchymal lesion of the kidney occur in the course of disease later stage.This disease generally has been mainly in family history male more than 30 years old, and clinical manifestation is an acute gouty arthritis: many nights and burst close to daybreak, get involved joint and big toe; Also can cause renal calculus and nephropathy: the kidney urate calculus blocks urinary system and causes renal colic and hematuria, and most of patients has renal hypertension and albuminuria, and minority can develop into renal failure.Gout has become one of the 21st century new urgency that faces of whole world disease to be controlled.
The general intermittent attack of gout mainly shows as position rednesses such as big toe joint, ankle joint and articulations digitorum manus during morbidity, and be attended by acupuncture, the sharp property pain as lancinating, the most of patients hyperpyrexia that also can occur together.The gout calculus will appear in the patient of the general course of disease above 5 years, the gout calculus can cause the joint gross distortion, the patient can't normally be walked, even can't hold every-day objects such as getting pen, book, chopsticks, tophus is treated untimely words ulceration voluntarily, wound is not healed year in year out, and finally can disable because of infection forces patient's amputation.Part patient also can be because of diseases such as the concurrent coronary heart disease of gout, hypertension, diabetes.Especially the course of disease surpasses the gouty nephropathy patient more than 10 years, if the state of an illness is not controlled, is easy to cause renal colic, hematuria kidney until causing renal failure and uremia, and final, the patient who has has to rely on renal transplantation to earn a bare living.
On therapeutics, antigout drug is primarily aimed at the pathophysiological mechanism that gout takes place, and can synthesize, promote urate excretion or inflammation-inhibiting reaction to bring into play the gout effect by suppressing uric acid.Non-salicylic acid NSAID (non-steroidal anti-inflammatory drug) and colchicine are mainly adopted in the treatment of gout acute attack, and the main therapeutic purposes of chronic gout are to reduce uric acid content in the blood, probenecid commonly used and allopurinol etc.Yet these medicines are all limited because of curative effect, the big clinical practice of untoward reaction is limited.Therefore, still there is not ideal gout treatment medicine clinically.
Gouty arthritis (
Gouty arthritis, be to increase GA), thereby urate crystal is deposited on a kind of metabolic osteoarthritis that the joint causes by blood uric acid concentration due to the purine metabolism obstacle.Uric acid sodium (monsodium urate, MSU) crystal is proved to be the non-microorganism sexually transmitted disease (STD) substance of GA, and its inductive immune inflammation plays an important role in the morbidity of GA.
Acute GA outbreak is mainly by synovial membrane inflammatory cell infiltration, uric acid deposition, tissue local necrosis, early stage urate crystal comes off from the synovial membrane of calmness and enters the synovial fluid, protein in the synovial fluid is adsorbed in crystal surface immediately, and engulfed by synovial cell, multinuclear leucocyte, monocyte, macrophage, due to the synovial membrane surface congestion and edema, cell infiltration.On therapeutics, at present medicine such as on-steroidal AID, colchicine etc. are all limited or the heavier clinical practice of untoward reaction is limited because of curative effect.Therefore, it is significant to continue to explore the high-efficiency low-toxicity medicine for the treatment of acute GA.
The Chinese herbal treatment ischemic diseases is with a long history, but according to modern medicine, especially evidence-based medicine EBM standard, still do not have conclusive evidence at present.If can find a kind of effective angiogenesis promoting chemical compound from the Chinese herbal medicine active component, this is significant to the treatment that explanation and this chemical compound of Chinese herbal treatment ischemic diseases are used for ischemic diseases.
Icariin (Icariin) is a kind of known compound, molecular formula: C
33H
40O
15, its structural formula is:
This chemical compound is the dry stem and leaf extract of Berberidaceae plant Herba Epimedii Epimedium brevicornum Maxim., arrow leaf Herba Epimedii Epimedium sagittatum Maxim., pubescence Herba Epimedii Epimedium pubescens Maxim., Epimedium wushanense Epimedium wushanense T.S.Ying or Herba Epimedii Epimedium koreanum Nakai.
Known this chemical compound has the cardiovascular and cerebrovascular vessel of increasing blood flow, promotes hemopoietic function, improves effects such as immunologic function and bone metabolism, has effects such as kidney invigorating and YANG supporting, defying age, antitumor.Icariin can promote that sexual function is that the gonepoiesis of cloudy gas section office is hyperfunction, after seminal vesicle is full of, and sensation nerve, indirect excitation libido and causing.Icariin can be old and feeble machine-processed from the influence of different aspects, as influence passage, prolongs trophophase, regulates immunity and excretory system, improves organism metabolism and each organ dysfunction.At cardiovascular system, icariin has certain protective role to the rat heart muscle ischemia that pituitrin causes, has tangible hypotensive effect.In addition, effect such as that icariin also has is antibacterial, antiviral, antiinflammatory, and effects such as blood fat reducing, hypoglycemic activity and antitumor.But the report that does not still have gout so far.
Summary of the invention
The objective of the invention is: the application of a kind of icariin in the preparation anti-gout drugs is provided, and it finds that icariin has the effect of gout, particularly has preventive and therapeutic effect to acute gouty arthritis.
The present invention is achieved in that the application of icariin in the preparation anti-gout drugs.
In order to verify technique effect of the present invention,, observed the prevention effect of ICA to this model by rat acute gouty arthritis (hereinafter to be referred as the GA) model that adopts joint cavity injection uric acid sodium (luring) to lead hereinafter to be referred as MSU.
Material
1.1 animal
72 of SD rats, male female half and half, body weight 200-250g.Big level ground hospital of Third Military Medical University animal center provides, animal credit number: SCXK(Chongqing) 2012-0005.
Instrument
BS-110S type electronic analytical balance (Beijing Sai Duolisi balance company limited); HH.W21.420 type electric heating constant temperature water temperature case (Beijing with bright Medical Instruments factory); F45-30-11 type High speed refrigerated centrifuge (German Eppendorf company); Ultrasonic machine (Shanghai hat hypersonic sound Instr Ltd.).BM4000B microscope (German Leica company), paraffin slicing machine (U.S. Sandon company).
Reagent and reagent
For this Chinese mugwort institute of Chinese materia medica, HLPC identifies purity to ICA available from Nanjing〉98%, colchicine is Yunnan pharmaceutical Co. Ltd of a Wu nation product, lot number: 090105, MSU is available from U.S. sigma company.
Method
2.1 animal grouping and administration
The laboratory animal adaptability is divided into 6 groups by sex after raising 7d at random, be respectively blank group, model group, ICA low (20mg/kg), in (40mg/kg), high (80mg/kg) dosage group, positive drug group (colchicine, 0.15mg/kg), totally 6 groups, every group 12, gastric infusion 7d, normal control group and model group give the equivalent distilled water and irritate stomach.
The preparation of solution
Will 3g MSU add and boil in the 100mL distilled water and fully stir, treat that MSU dissolves fully after, handle by ultrasonication, be configured to the 3.0%MSU solution for standby.
Modeling
1 h modeling after the administration in the 5th day, lumbar injection chloral hydrate (35mg/kg) anesthesia, each is organized rat and lies on the back fixing, iodophor disinfection right hind ankle joint, be inserted into tibia tendon inboard from 45 ° of directions with No. 6 entry needles behind at the rat right hind leg ankle joint, feel to have and fall through after the sense, inject volume fraction 3.0%MSU solution 100 μ L, heaving with the joint capsule offside is the injection standard, prepares acute GA model.Matched group right hind ankle joint injection equal-volume normal saline
[1]
Calculate rat swollen joint expansibility
36h measures the same position Zhou Jing of right hind ankle joint with the thread method after preceding 1 h of modeling and the modeling, calculates the swelling rate according to following formula.Limb ankle joint Zhou Jing * 100% before and after swelling rate (%)=(cause scorching back hind leg ankle joint Zhou Jing-cause scorching before and after limb ankle joint Zhou Jing)/cause is scorching.
Rat behavior is learned scoring
After the modeling, every 9h, 18h, 27h, 36h observe uncle's gait, standards of grading
[8]: 0 is divided into normal gait, and biped evenly lands; 1 is divided into slight limping, and it is slightly crooked to be tried lower limb; 2 are divided into moderate walks lamely, and is tried lower limb and has just touched ground; 3 are divided into severe walks lamely, and is tried the lower limb built on stilts, the tripodia walking that lands.
Leukocytic detection in the rat serum routine
Randomly draw 5 rats and get its blood and carry out routine blood test and detect in every big group, the variation tendency of observing every group of rat leukocyte is analyzed ICA to the effect of its inflammation because of cell.
Ankle joint chamber hydrops smear
Insert and extract hydrarthrosis with No. 5 syringe needles behind at rat right hind leg swelling ankle joint, the hydrarthrosis that extracts is coated with uniformly is taken on the microscope slide haematoxylin-Yihong (HE) dyeing, observation ankle joint hydrops cell infiltration situation under the light microscopic.
The observation of rat ankle joint pathological change:
Put to death behind the modeling 36h and respectively organize rat, get its ankle joint and fix in 10% neutral formalin solution, solution is fixed, and EDTA-2NA solution carries out decalcification, conventional dehydration, transparent, embedding, section and haematoxylin-Yihong (HE) dyeing, light microscopic is observed local histopathology down and is changed.
The result
3.1 ICA induces the influence of rat acute GA ankle swelling rate to MSU solution
36h has measured the same position Zhou Jing of rat right hind leg ankle joint after preceding 1h of modeling and the modeling, and calculates its arthroncus rate.Found that, the no swelling of blank group, model group occur obvious swelling (
p＜0.01), the swelling rate is 60%, and the modeling success is described.Yet, the middle and high dosage group of ICA to and positive drug group (colchicine) curative effect similar, its swelling rate obviously reduces (all than model group
p＜0.05), as shown in Figure 1.
Fig. 1 annotates: blank group compares with model group:
* p＜0.01; each treatment group and model group compare:
# p＜0.05.
MSU solution is induced the ethological influence of rat acute GA gait
Model group activities in rats minimizing behind the 9h after the modeling, the right hind bending, not too unusual, show as limping in various degree, scoring significantly raises, and 27h cashes the most obvious, lasts till 36h.Compare with model group, middle and high dosage group of ICA and positive drug group activities in rats state significantly improve, and scoring effectively reduces (seeing Table 1).
To the conventional leukocytic influence of rat serum
The blank group quantity of leucocyte of model group animal obviously increases.Model group and each medicine group compare, and the middle and high dosage group of ICA quantity of leucocyte all has obvious reduction, with positive drug group (colchicine) therapeutic equivalence, as shown in Figure 2.
Fig. 2 annotates: blank group compares with model group:
* p＜0.05; each treatment group and model group compare:
# p＜0.05.
MSU solution is induced rat acute GA synovial tissue and the pathological influence of ankle joint hydrops
Synovial membrane pathological observation result shows that blank group rat ankle joint synovial membrane and surrounding tissue are normal, no inflammatory cell infiltration; Model group rat ankle joint inflammation is more remarkable, synovial membrane rough surface injustice, and congestion and edema, visible a large amount of inflammatory cell infiltration, synovial membrane present the hypertrophy sample and change; Each dosage group of ICA and positive drug (colchicine) group ankle joint inflammation is alleviating in various degree all, and surrounding soft tissue's hyperemia is not remarkable, sees a small amount of inflammatory cell infiltration, as shown in Figure 3.Ankle joint hydrops pathological observation result shows, find a large amount of inflammatory cells and intensive in the model group rat ankle joint hydrops, each dosage group of ICA all has alleviating in various degree, middle and high dosage group to see a small amount of inflammatory cell and loose to rat ankle joint hydrops inflammatory cell, as shown in Figure 4.
Fig. 3 annotates: A, blank group; B, model group; C, the ICA low dose group; D, dosage group among the ICA; E, the ICA high dose group; F, the positive drug group.
Fig. 4 annotates: A, model group; B, the ICA low dose group; C, dosage group among the ICA; D, the ICA high dose group.
Discuss
Acute GA is that urate crystal is deposited on tissues such as joint capsule, synovial membrane, cartilage and sclerotin because of the blood uric acid increases, and stimulates the joint and the ankle joint synovial membrane that causes and the pathology damage and the inflammatory reaction of surrounding tissue.MSU is used to one of method of inducing by rat acute GA model at Chang Zuowei instrument medicine medically, and this method has simply, reaches fast the success rate advantages of higher.Therefore, this experiment adopts this method to duplicate acute GA model.Found that carrying out property of gait scoring increases, the obvious swelling in pathological changes joint, prompting modeling success.
At present, anti-gout drugs mainly contains and suppresses the synthetic medicine of uric acid such as other purine, the medicine of increase uric acid discharge such as medicine such as the colchicine and the nonsteroidal antiinflammatory drug etc. of probenecid and inhibition leukoplania, but all there is untoward reaction in various degree in these medicines, thereby clinical practice is limited.ICA is the main effective ingredient of the flavonoid of Chinese medicine Herba Epimedii, has and discovers that ICA is a kind of natural anti-inflammatory drug.This experiment finds that ICA can obviously improve the ankle joint synovial membrane pathological lesion that acute GA rat model ankle swelling degree and MSU cause, reduce the gait scoring, blood and hydrarthrosis inflammatory cell infiltration are clearly better, show that ICA has certain preventive and therapeutic effect to the rat acute GA due to the MSU, showed that there is good potential applicability in clinical practice in ICA aspect the acute GA of treatment, is worth further further investigation.
The present invention finds that icariin has preventive and therapeutic effect to gouty arthritis, comprises acute gouty arthritis and chronic gout joint, and proves by zoopery, and icariin can alleviate uric acid sodium really and induce acute gouty arthritis.Therefore icariin is used to prepare anti-gout drugs, can be the treatment gout a kind of natural drug is provided, thereby reduce the untoward reaction of using anti-gout drugs to cause, excavate the new purposes of specificity monomer icariin on gout in the known Chinese herbal medicine Herba Epimedii, opened up new application.The further research though its mechanism is still needed,, the present invention be used for acute GA for ICA follow-up study the basic pharmacology foundation is provided.Material source of the present invention is extensive, is easy to obtain, be used to prepare medicine simple, have a better therapeutic effect.
Description of drawings
Fig. 1 for ICA to MSU induce rat acute GA ankle swelling rate influence (
± s, n=12);
Fig. 2 ICA to the influence of the rat leukocyte of MSU solution inductivity GA ankle joint (
± s, n=5);
Fig. 3 rat ankle joint synovial membrane HE picture that dyes;
Fig. 4 rat ankle joint hydrops HE picture that dyes.
The specific embodiment
Embodiments of the invention 1: get icariin 5g, medical starch 75 g, microcrystalline Cellulose 20 g, medical starch is dry earlier, cross 120 mesh sieves, mix with icariin, microcrystalline Cellulose again, cross twice 120 mesh sieves, insert in the hard capsule, make 1000 capsules of the present invention.Every hard capsule contains principal agent composition 0.5 mg.
Embodiments of the invention 2: icariin 5g, hypromellose 6g, carboxymethylstach sodium 10g, microcrystalline Cellulose 8g, lactose 115g, starch 50g, magnesium stearate 1g; To drop into behind principal agent and the abundant mixing of adjuvant in the homogenizer, it is an amount of that spraying adds water, granulate, and moisture Control is 3 ~ 4%, and tabletting is made 1000 then, the bag film-coat.
Embodiments of the invention 3: icariin 5g, add the dissolving of 400 ml Macrogol 200s, add an amount of distilled water again and dilute, and then add an amount of sucrose and adjust volume to 1000 ml, stir evenly, filter, fill becomes every of 10 ml or 20 ml, sterilization packaging.
Claims (1)
1. the application of icariin in preparation treatment gout medicine.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107048199A (en) * | 2017-04-12 | 2017-08-18 | 山东菌芝堂生物科技发展有限公司 | A kind of instant porridge for recovering Patients with Hyperuricemia gut flora balance and preparation method thereof |
| CN108714165A (en) * | 2018-07-03 | 2018-10-30 | 泓博元生命科技（深圳）有限公司 | A kind of improvement gout composition, preparation and preparation method thereof |
| CN108926573A (en) * | 2018-07-03 | 2018-12-04 | 泓博元生命科技（深圳）有限公司 | A kind of NADH composition and preparation method and application reducing uric acid index |
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Address after: 563000 No. 201, Dalian Road, Zunyi, Guizhou Patentee after: ZUNYI MEDICAL University Address before: 563000 No. 201, Dalian Road, Zunyi, Guizhou Patentee before: ZUNYI MEDICAL University |
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Effective date of registration: 20220620 Address after: 537023 Ma Lu Ling, Shihe Town, Fumian District, Yulin City, Guangxi Zhuang Autonomous Region Patentee after: Guangxi Shenli Pharmaceutical Co.,Ltd. Address before: 563000 No. 201, Dalian Road, Zunyi, Guizhou Patentee before: ZUNYI MEDICAL University |